Chronic renal failure (CRF) may result from any major cause of renal dysfunction. The most common cause of end-stage renal discease is diabetic nephropathy, followed by hypertensive nephroangiosclerosis and various primary and secondary glomerulopathies. The functional effects of CRF can be categorized as diminished renal reserve, renal insufficiency (failure), and uremia.
Lassitude, fatigue, and decreased mental acuity often are the first manifestations of uremia. In addition, other symptoms of CRF include neuromuscular features, anorexia, nausea, vomiting, stomatitis, an unpleasant taste in the mouth, malnutrition, GI ulceration, bleeding, cardiomyopathy (hypertensive, ischemic), and ultimately congestive heart failure or dependent edema.
Treatments for CRF include protein restriction, ACE inhibitors, possibly angiotensin receptor blockers, and meticulous attention to diet as CRF progresses from moderate to end-stage disease. When conventional therapy is no longer effective, the patient is considered to have end-stage renal disease (ESRD) and long-term dialysis or transplantation is an option. Most physicians agree that uremic symptoms (nausea, vomiting, anorexia, fatigability, diminished sensorium) and signs (pericardial friction rub, refractory pulmonary edema, metabolic acidosis, foot or wrist drop, asterixis) necessitate urgent dialysis.
Dialysis is the process of removing toxins directly from the blood (hemodialysis) or indirectly via peritoneal fluid (peritoneal dialysis) using diffusion across a semipermeable membrane. Simultaneous ultrafiltration is usually accomplished to remove accumulated fluid ordinarily excreted by functioning kidneys. A dialysis regimen for ESRD should improve the patient's ability to perform activities of daily living, improve comfort, allow the patient to eat a reasonable diet, help maintain a normal blood pressure, and prevent progression of uremic neuropathy. Most ESRD patients require hemodialysis thrice weekly to maintain a state of well-being. Early treatment typically takes three to five hours in adults and three to four hours in children. Blood is removed from the patient via a suitable vascular access and pumped to the membrane unit. The dialysate compartment of the membrane unit is under negative pressure relative to the blood compartment, which permits hydraulic ultrafiltration of excess total body fluid across the membrane. Dialyzed blood is returned to the patient through tubing with an air embolus protector. The most common complications during hemodialysis are, in descending order of requency, hypotention (20-30% of dialyses), cramps (5-20%), nausea and vomiting (5-15%), headache (5%), chest pain (2-5%), back pain (2-5%), itching (5%), and fever and chills (&lt;1%).
Hypotension during dialysis is a very common event and is primarily a reflection of the large amount of fluid relative to the plasma volume that is removed during an average dialysis session. Maintenance of blood volume during dialysis depends on rapid refilling of the blood compartment from surrounding tissue spaces. A decrease in the blood volume can result in decreased cardiac filling, which in turn can cause reduced cardiac output and, ultimately, hypotension.
In addition, hypotension maybe related to lack of vasoconstriction. Blood volume depletion causes a state in which cardiac output is limited by cardiac filling. Any minor decrease in peripheral vascular resistance or decrease in cardiac filling can precipitate hypotension, because the cardiac output cannot increase in a compensatory manner. Under conditions of decreased cardiac filling, increases in heart rate have little effect on cardiac output. The hypotension may also relate to cardiac factors such as diastolic dysfunction, heart rate and contractility. In addition, it has been suggested that nitric oxide may play a role in hypotension. Yokokawa, Joji, et. al., Increased Nitric Oxide Production in Patients with Hypotension during Hemodialysis, Ann. Intern. Med. 1995; 123: 35-37; Lin, Shih-Hua, et. al., Increased Nitric Oxide Production in Hypotensive Hemodialysis Patients, ASAIO Journal 1996; 42 no. 5: M895-M899; Rysz, Jacek, et al., Nitric Oxide Release in the Peripheral Blood During Hemodialysis, Kidney International, 1997; 51; 294-300; Nishimura, Masato, et. al., Enhanced Production of Nitric Oxide May be Involved in Acute Hypotension During Maintenance Hemodialysis, American Journal of Kidney Diseases, 1998, 31 no 5; 809-817. Management of the acute hypotensive patient includes placement of the patent in the Trendelenburg position (if respiratory status allows this). A bolus of 0.9% saline (100 ml or more as necessary) may be rapidly administered through the venous blood line. The ultrafiltration rate may also be reduced to as near zero as possible. Ultrafiltration can be resumed (at a slower rate, initially) once vital signs have stabilized. As an alternative to 0.9% saline, hypertonic saline, glucose, mannitol, or albumin solutions can be used to treat the hypotensive episode.
While hypotension remains the most prevalent side effect of hemodialysis and although its incidence has diminished with the advent of more advanced dialysis technology, the management treatments described above are not wholly satisfactory. For example, they include interruption of dialysis for a period to allow for blood pressure normalization. Thus, there is a continuing need for an alternative treatment for hypotension consequent to hemodialysis.